Anatomical-Ultrasound Visor for Regional Anaesthesia.

INTRODUCTION: Regions considered optimal for performing peripheral nerve blocking have been well documented. However identify and perform regional anesthesia in those regions from ultrasound images remains a challenge. AIM: This study aims to develop a virtual environment for the simulation of ultrasound exploration of the neck nerves and both the upper and lower limbs for regional anesthesia. METHOD: Cross-sectional images were obtained from Magnetic Resonance Imaging for puncture regions involved in ultrasound-guided nerve block. RESULTS: A three-dimensional digital viewer was developed for the anatomical and ultrasound identification of key structures involved in peripheral nerve block in neck, upper and lower limbs. CONCLUSION: This study provides a virtual environment software used to simulate ultrasound exploration of nerve neck and upper and lower limbs for regional anesthesia. DISCUSSION: Potential implications of this tool for improving the ultrasound exploration for regional anesthesia and acquisition of anatomical knowledge are further discussed.

Influence of UGT2B7, CYP3A4, and OPRM1 Gene Polymorphisms on Transdermal Buprenorphine Pain Control in Patients with Critical Lower Limb Ischemia Awaiting Revascularization.

BACKGROUND: Pain control in critical limb ischemia (CLI) varies considerably between individuals. OBJECTIVE: To evaluate pharmacogenetically the response to transdermal buprenorphine (BUP-TTS) in patients with CLI who are awaiting revascularization. METHODS: One hundred and seven patients with CLI were treated with BUP-TTS. The following were analyzed: (1) pain perception (visual analog scale (VAS) before and 4 days after treatment) and (2) genetics: glucuronosyltransferase (UGT2B7), cytochrome (CYP3A4), and µ-opioid receptor (OPRM1) gene polymorphisms. RESULTS: Ninety-three patients completed the study. The VAS score by the fourth day of analgesia dropped from 6.82 to 3.38 (P < 0.05). The analgesic response to BUP-TTS was greater in men than in women (P = 0.019). Patients who were AA homozygotes for the CYP3A4 gene showed the best response to analgesic treatment (P = 0.003). The combination of the CYP3A4 gene with UGT2B7 or OPRM1 was favorable to the effect of the CYP3A4 gene (P = 0.045 and P = 0.026, respectively). The combination of UGT2B7 with OPRM1 was ineffective (P = 0.648). The 3 polymorphisms together had no effect on response to treatment (P = 0.461). CONCLUSIONS: BUP-TTS is efficacious in the control of pain in patients with CLI. The homozygous AA carriers of the CYP3A4 gene respond better to treatment with BUP-TTS.

Influence of uridine diphosphate-glucuronyltransferase 2B7 (UGT2B7) variants on postoperative buprenorphine analgesia.

BACKGROUND: Genetic factors are known to influence individual differences in pain and sensitivity to analgesics. Different genetic polymorphisms in opioid-metabolizing enzymes that can affect the analgesic response to opioids have been proposed. This study investigates a possible difference in the response to postoperative buprenorphine analgesia related to the presence of different isoforms (cytosine or thymine substitution at nucleotide 802) of UGT2B7 gene. METHODS: Transdermal buprenorphine was administered to 91 patients who underwent muscle-sparing thoracotomy. UGT2B7 polymorphism at locus C802T (His268Tyr) was detected using a PCR Taqman-based procedure. The severity of postoperative pain at rest and during coughing or deep inspiration was assessed by visual analog scale score after surgery. Hospital stay and perioperative opioid consumption were collected. RESULTS: Genotype frequencies were 18.4% for UGT2B7*1/*1, 52.9% for UGT2B7*1/*2, and 28.7% for UGT2B7*2/*2. VAS pain scores at rest were statistically similar among the groups except at 24, 60, and 120 hours (UGT2B7*2/*2 genotype showing higher pain scores). Patients with the UGT2B7*2/*2 genotype showed higher VAS scores triggered by coughing after the 48 hours (P < 0.05). In addition, patients with this genotype reported a higher prevalence of severe pain after 48 postoperative hours (P < 0.05). Thirty-eight percent of patients carrying genotype UGT2B7*2/*2 experienced severe pain in a final survey vs. 17% in the group with UGT2B7*1/*1 (P = 0.36). CONCLUSIONS: The presence of the SNP 802C>T UGT2B7 (UGT2B7*2/*2) is associated with a worse analgesic response to transdermal buprenorphine in the postoperative period of thoracic surgery.

Análisis de polimorfismos del gen TRPV1 en pacientes españoles con dolor neuropático / Analysis of TRPV1 gene polymorphisms in Spanish patients with neuropathic pain

Fundamento y objetivo: El receptor vanilloide TRPV1 es un integrador molecular de los estímulos dolorosos. Varios estudios recientes sugieren que TRPV1 puede desempeñar un papel importante en el desarrollo y mantenimiento del dolor crónico. En un intento por determinar si las variaciones genotípicas del gen TRPV podrían estar involucradas en la susceptibilidad a sufrir dolor neuropático, hemos analizado variantes polimorfas del gen TRPV1 humano. Pacientes y método: Hemos estudiado los genotipos Met315Ile e Ile585Val del gen TRPV1 en un total de 440 sujetos de raza caucásica: 232 pacientes diagnosticados de dolor neuropático y 208 voluntarios sanos emparejados por edad y sexo. Los polimorfismos se analizaron mediante reacción en cadena de la polimerasa con sondas TaqMan específicas para cada uno de los alelos. Resultados: Hemos observado una distribución similar de los genotipos Met315Ile e Ile585Val en pacientes con dolor neuropático y en sujetos sanos. Sin embargo, el genotipo Met315Met es más frecuente en las mujeres diagnosticadas de dolor neuropático. No se observaron diferencias significativas cuando se segrega a los pacientes en función de los valores obtenidos mediante la escala visual analógica. Conclusiones: La observación de diferencias en la distribución de genotipos Met315Ile de TRPV1, solo en las mujeres diagnosticadas de dolor neuropático, sugiere que este polimorfismo, junto con otros factores específicos de sexo, pueden influir en la susceptibilidad individual a sufrir dolor neuropático (AU)

Background and objective: The vanilloid receptor TRPV1 is a molecular integrator of painful stimuli. Several recent studies suggest that TRPV1 may play a role in development and maintenance of chronic pain. In an attempt to determine if genotypic variations in TRPV1 gene could be involved in the susceptibility to suffer neuropathic pain we have studied genetic variants of human TRPV1 gene.Patients and methods: We have studied the distribution of Met315Ile and Ile585Val TRPV1 polymorphisms in a total of 440 Caucasian subjects: 232 patients with neuropathic pain and 208 healthy subjects matched by age and sex. The polymorphisms were analyzed with polymerase chain reaction (PCR) using TaqMan probes specific for each allele. Results: Our results show that the distribution of Met315Ile and Ile585Val genotypes and alleles is similar in patients with neuropathic pain and in healthy subjects. However, the Met315Met genotype is more frequent in females diagnosed as suffering neuropathic pain. No differences were observed when we segregate the patients according to visual analogue scale values. Conclusions: The observation of differences in the distribution of Met315Ile TRPV1 genotypes only in females diagnosed of neuropathic pain suggests that this polymorphism, together with other physiological factors such as sex, may influence individual susceptibility to neuropathic pain (AU)

[Analysis of TRPV1 gene polymorphisms in Spanish patients with neuropathic pain]. / Análisis de polimorfismos del gen TRPV1 en pacientes españoles con dolor neuropático.

BACKGROUND AND OBJECTIVE: The vanilloid receptor TRPV1 is a molecular integrator of painful stimuli. Several recent studies suggest that TRPV1 may play a role in development and maintenance of chronic pain. In an attempt to determine if genotypic variations in TRPV1 gene could be involved in the susceptibility to suffer neuropathic pain we have studied genetic variants of human TRPV1 gene. PATIENTS AND METHODS: We have studied the distribution of Met315Ile and Ile585Val TRPV1 polymorphisms in a total of 440 Caucasian subjects: 232 patients with neuropathic pain and 208 healthy subjects matched by age and sex. The polymorphisms were analyzed with polymerase chain reaction (PCR) using TaqMan probes specific for each allele. RESULTS: Our results show that the distribution of Met315Ile and Ile585Val genotypes and alleles is similar in patients with neuropathic pain and in healthy subjects. However, the Met315Met genotype is more frequent in females diagnosed as suffering neuropathic pain. No differences were observed when we segregate the patients according to visual analogue scale values. CONCLUSIONS: The observation of differences in the distribution of Met315Ile TRPV1 genotypes only in females diagnosed of neuropathic pain suggests that this polymorphism, together with other physiological factors such as sex, may influence individual susceptibility to neuropathic pain.

The comparative abilities of propofol and sevoflurane to modulate inflammation and oxidative stress in the kidney after aortic cross-clamping.

BACKGROUND: Propofol has been reported to provide protection against ischemia-reperfusion injury. Nuclear transcription factor kappa B (NFkappaB) plays a key role in oxidative stress and the inflammatory response during ischemia-reperfusion. We compared the effect of propofol with sevoflurane on kidney NFkappaB expression and systemic inflammatory responses induced by aortic clamping. METHODS: Twenty piglets were divided into four groups: sham surgery group with propofol (group SP, n = 5); sham group with sevoflurane (group SS, n = 5); and suprarenal clamping for 30 min with aorta-aortic bypass under propofol (group CP, n = 5) or sevoflurane (group CS, n = 5) anesthesia. Propofol was administered at 4 mg x kg(-1) x h(-1) i.v. and sevoflurane given at 1.5% inspiratory concentration. Peripheral blood and kidney biopsies were taken before the start of surgery, 15 min after unclamping the aorta, 24, 48, 72 h, and 7 days after surgery. Plasma creatinine, myeloperoxidase, tumor necrosis factor-alpha, interleukin 1-beta; and kidney superoxide anion and superoxidase dismutase were measured. The expression of inducible nitric oxide synthase and renal tissue NFkappaB was measured using Western blotting. RESULTS: Compared with the CS group, animals in the CP group had lower concentrations of myeloperoxidase, tumor necrosis factor-alpha, interleukin 1beta, superoxide anion, superoxidase dismutase (P < 0.05) from 24 to 72 h after surgery and diminished NFkappaB expression and inducible nitric oxide synthase activity (P < 0.05) at 48 and 72 h after surgery, respectively. CONCLUSIONS: Compared with sevoflurane, propofol administration during suprarenal aortic clamping and unclamping led to modulation of markers of inflammation and decreased NFkappaB expression.

Laboratory investigation: effects of propofol on the systemic inflammatory response during aortic surgery.

PURPOSE: A laboratory investigation was undertaken to assess the effects of propofol on renal function, through modulation of the systemic inflammatory response, in an in vivo experimental model of aortic surgery in comparison with sevoflurane. METHODS: Twenty young male piglets were anesthetized with either propofol 4 mg.kg(-1).hr(-1) (n = 10) or sevoflurane 1.5% end-tidal concentration (n = 10). Animals were subjected to aorta-aortic bypass with suprarenal aortic clamping for 30 min. At specific intervals (basal -before the start of surgery; reperfusion 15 min after unclamping the aorta; at 24, 48 and 72 hr after surgery, and on the seventh day after surgery) the levels of the following were determined: plasma creatinine, renal myeloperoxidase, tumour necrosis factor-alpha, interleukin 1-ss, and interferon-gamma; kidney superoxide anion and its detoxifying enzyme superoxidase dismutase, kidney malondialdehyde and the activity of inducible nitric oxide synthase. Seven days after surgery, the animals were anesthetized using the described techniques, and after blood withdrawal and kidney sampling they were sacrificed. RESULTS: In comparison with sevoflurane, propofol was associated with a lower concentration of plasma creatinine (P < 0.05) together with lower concentrations of myeloperoxidase, tumour necrosis factor-alpha, interleukin 1-ss, interferon-gamma, superoxide anion and superoxidase dismutase, malondialdehyde and inducible nitric oxide synthase (P < 0.05). CONCLUSION: In an experimental model of aortic reconstructive surgery, and compared with sevoflurane, propofol anesthesia is associated with less neutrophil infiltration, lower plasma proinflammatory cytokine levels, lower production of oxygen free radicals, less lipid peroxidation, and reduced inducible nitric oxide synthase activity. These observations suggest a possible renal protective effect of propofol in this surgical setting.

Effectiveness and tolerability of the buprenorphine transdermal system in patients with moderate to severe chronic pain: a multicenter, open-label, uncontrolled, prospective, observational clinical study.

BACKGROUND: A new transdermal delivery system (TDS) for the rate-controlled systemic delivery of buprenorphine is available in 3 patch strengths, with release rates of 35, 52.5, and 70 microg/h over 72 hours, delivering daily amounts of 0.8, 1.2, and 1.6 mg, respectively. Randomized, double-blind, placebo-controlled, Phase III clinical trials in >400 patients with severe pain of malignant or nonmalignant origin have shown the analgesic efficacy of buprenorphine TDS. OBJECTIVE: This study investigated the effectiveness and tolerability of buprenorphine TDS for the relief of chronic pain in routine clinical practice. METHODS: This was a multicenter, open-label, uncontrolled, prospective, observational, 3-month follow-up study in patients who were beginning buprenorphine TDS treatment for moderate to severe cancer or noncancer pain that had not responded to nonopioid analgesics. Patches were to be changed every 72 hours. Patients were evaluated at 1 and 3 months after the start of treatment. Those who dropped out were considered treatment failures. Pain relief was assessed on a 5-category verbal rating scale, and quality of life was assessed using the European Quality of Life 5D (EQ-5D) questionnaire. Tolerability was determined based on adverse events recorded during the follow-up period. RESULTS: The study recruited 1223 patients, most of whom were outpatients. Of the 1212 patients for whom sex data were available, 820 (67.7%) were women. In the 1188 patients with age data, the mean (SD) age was 64.9 (12.9) years. In the 1175 patients with data on the etiology of pain, 82.4% had noncancer pain. Six hundred eighty-eight (56.3%) patients completed the 3-month follow-up period. The median daily amount of buprenorphine TDS received at the beginning of the study was 0.8 mg (corresponding to 35 microg/h). Over the study period, there was a significant increase in the proportion of patients reporting very good or good pain relief (P < 0.001), from 3.6% (43/1205) at baseline to 63.2% (762/1205) after 1 month and 56.8% (685/1205) after 3 months. Quality of life also improved, from a mean (SD) EQ-5D score of 40.6 (20.5) at baseline to 56.8 (23.5) at 3 months (P < 0.001). Five hundred seventeen (42.3%) of the original 1223 patients experienced adverse events; the investigator judged 397 (32.5%) of these events possibly or probably related to study drug. The likelihood of experiencing a drug-related adverse event was greater in noncancer patients than in cancer patients. The most common adverse events were nausea (11.0%), vomiting (9.2%), and constipation (7.8%); the most common local adverse events were pruritus (1.4%), dermatitis (1.3%), and erythema (1.3%). CONCLUSION: In the population studied, buprenorphine TDS was effective in alleviating cancer and noncancer pain and was well tolerated overall.

COMT (Val158Met) polymorphism is not associated to neuropathic pain in a Spanish population.

It is well known that the response to painful stimuli varies between individuals and this could be consequence of individual differences to pain sensitivity that may be related to genetic factors. Catechol-O-methyltransferase (COMT) is one of the enzymes that metabolize catecholamine neurotransmitters. Differences in the activity of COMT influence the functions of these neurotransmitters. A single nucleotide polymorphism (Val158Met) of COMT leads to a three to four fold reduction in the activity of the enzyme and has been associated to modifications in the response to a pain stressor. Neuropathic pain is a progressive nervous system disease due to an alteration of the peripheral or central nervous system. To elucidate the possible role of COMT polymorphism in the susceptibility to neuropathic pain, we have performed a case-control study in a Spanish population. Analysis of the (Val158Met) COMT polymorphism was performed by PCR amplification and DNA digestion with restriction enzymes. Our study concludes that functional Val158Met polymorphism of COMT gene is not associated to increased susceptibility to neuropathic pain.

Aspirin-like defect in platelet secretion on a patient undergoing cardiac valve and coronary graft surgery. Perioperative management.

We show the case of an adult male with a previous diagnosis of an 'aspirin-like' defect in platelet secretion responses scheduled for cardiac valve surgery. Perioperative management and bleeding prevention were made following experts' recommendations.

[Validation of the Spanish version of the Brief Pain Inventory in patients with oncological pain]. / Validación española del cuestionario Brief Pain Inventory en pacientes con dolor de causa neoplásica.

BACKGROUND AND OBJECTIVE: Our goal was to validate the Spanish version of the Brief Pain Inventory (BPI) questionnaire used to measure the intensity of oncological pain and its impact on activities of daily living in patients with cancer. PATIENTS AND METHOD: Patients with oncological pain were consecutively included in the study. These patients filled up the Spanish version of the BPI questionnaire (CBD) and the Rotterdam Symptom Checklist (RCSL) during the inclusion visit and again after 3-5 days (patients with clinically stable oncological pain) or after one month (patients with unstable oncological pain). RESULTS: 126 patients were assessed; 85.1% of them had suffered some episode of irruptive pain 24 hours prior to their inclusion in the study. 86.5% of patients fully completed the questionnaire. The CBD showed mild to moderate correlations with the patients perception of pain severity and with the presence of tumor dissemination. The <> dimension of the RCSL displayed the highest correlation with the dimensions of the BPI (<> and <>). The internal consistency and the test-retest reliability between dimensions were good (0.87 and 0.89) and low to moderate (0.53 and 0.77), respectively. The CBD questionnaire was found to be a tool capable of detecting changes in pain intensity. The changes observed in the two CBD dimensions between study visits fairly reflected the patients perceived changes in pain intensity. CONCLUSIONS: The Spanish version of BPI is valid for measuring the intensity of oncological pain and its impact on activities of daily living in conditions of usual clinical practice.

Validación española del cuestionario Brief Pain Inventory en pacientes con dolor de causa neoplásica / Validation of the spanish version of the brief pain inventory in patients with oncological pain

FUNDAMENTO Y OBJETIVO: Validar la versión española del cuestionario Brief Pain Inventory (BPI) para medir la intensidad del dolor de causa neoplásica y su impacto en las actividades de la vida diaria en pacientes con cáncer. PACIENTES Y MÉTODO: Se incluyó consecutivamente a pacientes con dolor de origen neoplásico. Los pacientes cumplimentaron los cuestionarios BPI (Cuestionario Breve del Dolor o CBD en español) y el Rotterdam Symptom Checklist (RSCL) en la visita de inclusión. El CBD se repitió a los 3-5 días en los pacientes clínicamente estables de su dolor de origen neoplásico y ambos cuestionarios se repitieron al mes en los pacientes no estables de su dolor. RESULTADOS: Se evaluó a 126 pacientes, el 85,1 per cent había sufrido algún episodio de dolor irruptivo en las 24 h previas al inicio del estudio. El 86,5 per cent de los pacientes completó el CBD en su totalidad. Las puntuaciones del CBD se correlacionaron con la percepción del paciente de la intensidad máxima del dolor y con la presencia de tumor diseminado. La dimensión 'síntomas psicológicos' del RSCL fue la que presentó mayor correlación con las dimensiones del CBD ('intensidad del dolor' e 'interferencia en las actividades'). La consistencia interna de las dimensiones fue buena (0,87 y 0,89), y la fiabilidad test-retest entre baja y moderada (0,53 y 0,77). El CBD ha demostrado ser un instrumento capaz de detectar cambios en el nivel de dolor. Los cambios observados en las dos dimensiones del CBD entre las dos visitas de estudio reflejan los cambios percibidos por el propio paciente en la intensidad del dolor. CONCLUSIONES: La versión española del CBD se mostró válida para medir la intensidad del dolor de causa neoplásica y su impacto en las actividades de la vida diaria, en condiciones de práctica clínica habitual (AU)